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Tacrolimus Causes H...
Tacrolimus Causes Hypertension by Increasing Vascular Contractility via RhoA (Ras Homolog Family Member A)/ROCK (Rho-Associated Protein Kinase) Pathway in Mice
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- Wang, Xiaohua (författare)
- Sun Yat Sen Univ, Affiliated Hosp 7, Ctr Kidney & Urol, Dept Nephrol, Shenzhen, Peoples R China.
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- Jiang, Shan (författare)
- Sun Yat Sen Univ, Affiliated Hosp 7, Ctr Kidney & Urol, Dept Nephrol, Shenzhen, Peoples R China.
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- Fei, Lingyan (författare)
- Sun Yat Sen Univ, Affiliated Hosp 7, Ctr Kidney & Urol, Dept Nephrol, Shenzhen, Peoples R China.
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- Dong, Fang (författare)
- Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou, Peoples R China.
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- Xie, Lanyu (författare)
- Nanchang Univ, Coll Clin Med, Nanchang, Jiangxi, Peoples R China.
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- Qiu, Xingyu (författare)
- Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou, Peoples R China.
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- Lei, Yan (författare)
- Sun Yat Sen Univ, Affiliated Hosp 7, Ctr Kidney & Urol, Dept Nephrol, Shenzhen, Peoples R China.
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- Guo, Jie (författare)
- Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou, Peoples R China.
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- Zhong, Ming (författare)
- Sun Yat Sen Univ, Affiliated Hosp 7, Ctr Kidney & Urol, Dept Nephrol, Shenzhen, Peoples R China.
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- Ren, Xiaoqiu (författare)
- Zhejiang Univ, Affiliated Hosp 2, Dept Radiat Oncol, Sch Med, Hangzhou, Peoples R China.
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- Yang, Yi (författare)
- Zhejiang Univ, Sch Med, Affiliated Hosp 4, Dept Nephrol, Yiwu, Peoples R China.
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- Zhao, Liang (författare)
- Zhejiang Univ, Sch Med, Natl Clin Res Ctr Child Hlth, Childrens Hosp, Hangzhou, Peoples R China.
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- Zhang, Gensheng (författare)
- Zhejiang Univ, Sch Med, Natl Clin Res Ctr Child Hlth, Childrens Hosp, Hangzhou, Peoples R China.
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- Wang, Honghong (författare)
- Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou, Peoples R China.
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- Tang, Chun (författare)
- Sun Yat Sen Univ, Affiliated Hosp 7, Ctr Kidney & Urol, Dept Nephrol, Shenzhen, Peoples R China.
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- Yu, Luyang (författare)
- Zhejiang Univ, Coll Life Sci, Inst Genet & Regenerat Biol, Hangzhou, Peoples R China.
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- Liu, Ruisheng (författare)
- Univ S Florida, Coll Med, Dept Mol Pharmacol & Physiol, Tampa, FL USA.
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- Patzak, Andreas (författare)
- Charite Univ Med Berlin, Inst Translat Physiol, Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.
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- Persson, Pontus B. (författare)
- Charite Univ Med Berlin, Inst Translat Physiol, Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.
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- Hultström, Michael, 1978- (författare)
- Uppsala universitet,Anestesiologi och intensivvård,Institutionen för medicinsk cellbiologi
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- Wei, Qichun (författare)
- Zhejiang Univ, Affiliated Hosp 2, Dept Radiat Oncol, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Radiat Oncol, Hangzhou, Peoples R China.
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- Lai, En Yin (författare)
- Sun Yat Sen Univ, Affiliated Hosp 7, Ctr Kidney & Urol, Dept Nephrol, Shenzhen, Peoples R China.;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou, Peoples R China.;Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou, Peoples R China.;Charite Univ Med Berlin, Inst Translat Physiol, Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.;Berlin Inst Hlth, Inst Translat Physiol, Berlin, Germany.
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- Zheng, Zhihua (författare)
- Sun Yat Sen Univ, Affiliated Hosp 7, Ctr Kidney & Urol, Dept Nephrol, Shenzhen, Peoples R China.;Sun Yat Sen Univ, Affiliated Hosp 7, Ctr Kidney & Urol, Dept Nephrol, Shenzhen, Peoples R China.
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Sun Yat Sen Univ, Affiliated Hosp 7, Ctr Kidney & Urol, Dept Nephrol, Shenzhen, Peoples R China Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Physiol, Hangzhou, Peoples R China. (creator_code:org_t)
- Ovid Technologies (Wolters Kluwer Health), 2022
- 2022
- Engelska.
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Ingår i: Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0194-911X .- 1524-4563. ; 79:10, s. 2228-2238
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: To provide tacrolimus is first-line treatment after liver and kidney transplantation. However, hypertension and nephrotoxicity are common tacrolimus side effects that limit its use. Although tacrolimus-related hypertension is well known, the underlying mechanisms are not. Here, we test whether tacrolimus-induced hypertension involves the RhoA (Ras homolog family member A)/ROCK (Rho-associated protein kinase) pathway in male C57Bl/6 mice. methods: Intra-arterial blood pressure was measured under anesthesia. The reactivity of renal afferent arterioles and mesenteric arteries were assessed in vitro using microperfusion and wire myography, respectively. Results: Tacrolimus induced a transient rise in systolic arterial pressure that was blocked by the RhoA/ROCK inhibitor Fasudil (12.0 +/- 0.9 versus 3.2 +/- 0.7; P<0.001). Moreover, tacrolimus reduced the glomerular filtration rate, which was also prevented by Fasudil (187 +/- 20 versus 281 +/- 8.5; P<0.001). Interestingly, tacrolimus enhanced the sensitivity of afferent arterioles and mesenteric arteries to Ang II (angiotensin II), likely due to increased intracellular Ca2+ mobilization and sensitization. Fasudil prevented increased Ang II-sensitivity and blocked Ca2+ mobilization and sensitization. Preincubation of mouse aortic vascular smooth muscle cells with tacrolimus activated the RhoA/ROCK/MYPT-1 (myosin phosphatase targeting subunit 1) pathway. Further, tacrolimus increased cytoplasmic reactive oxygen species generation in afferent arterioles (107 +/- 5.9 versus 163 +/- 6.4; P<0.001) and in cultured mouse aortic vascular smooth muscle cells (100 +/- 7.5 versus 160 +/- 23.2; P<0.01). Finally, the reactive oxygen species scavenger Tempol inhibited tacrolimus-induced Ang II hypersensitivity in afferent arterioles and mesenteric arteries. Conclusions: The RhoA/ROCK pathway may play an important role in tacrolimus-induced hypertension by enhancing Ang II-specific vasoconstriction, and reactive oxygen species may participate in this process by activating the RhoA/ROCK pathway.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- angiotensin II
- hypertension
- reactive oxygen species
- tacrolimus
- vasoconstriction
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Wang, Xiaohua
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Jiang, Shan
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Fei, Lingyan
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Dong, Fang
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Xie, Lanyu
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Qiu, Xingyu
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visa fler...
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Lei, Yan
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Guo, Jie
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Zhong, Ming
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Ren, Xiaoqiu
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Yang, Yi
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Zhao, Liang
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Zhang, Gensheng
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Wang, Honghong
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Tang, Chun
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Yu, Luyang
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Liu, Ruisheng
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Patzak, Andreas
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Persson, Pontus ...
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Hultström, Micha ...
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Wei, Qichun
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Lai, En Yin
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Zheng, Zhihua
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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Hypertension
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Uppsala universitet